System for global pandemic vaccine development challenged

Feb 6, 2007 (CIDRAP News) – Indonesia, the country that has seen more human deaths from avian influenza H5N1 than any other, has ceased sharing viruses isolated from its patients with international health authorities, challenging the global system for flu-strain identification and vaccine development.

The World Health Organization (WHO) has not received any viral isolates from Indonesia since the end of 2006, Dr. David Heymann, the agency's acting assistant director-general for communicable diseases, said in a telephone briefing this morning.

"We have been in discussions with the Ministry of Health since November of last year," he said. "We will continue to work with them and with all countries to ensure this virus will remain somehow a public good."

Indonesia is also preparing to sign on Wednesday an agreement giving a single vaccine manufacturer rights to its isolates, Heymann said—though by the end of the day Tuesday, it remained unclear whether the agreement with Baxter International would block health authorities and other manufacturers from accessing the samples, or solely guarantee Indonesia's right to purchase vaccines made from its viruses.

The episode highlights the fragile and increasingly contentious system by which flu viruses—from both seasonal flu and novel strains such as avian influenza H5N1—are identified and shared around the world.

Under that system, designed by the WHO with the agreement of its 193 member states, flu viruses are isolated in a country and analyzed to increasing levels of sophistication by a national lab, regional lab, and 1 of 4 WHO Influenza Collaborating Centers in Tokyo, Melbourne, London, and the US Centers for Disease Control and Prevention in Atlanta.

Gene sequences from the analyses are used to identify emerging strains of flu—to track the evolution of the disease and, crucially for Tuesday's news, to provide the basis for flu vaccines made by pharmaceutical companies.

For about 50 years, the system has operated on goodwill, with its costs borne by the WHO membership and no compensation offered for viral contributions. There have been signs in recent months, though, that the agreement is breaking down.

China last year refused for a time to share flu virus samples internationally, complaining that credit for discoveries was going to Western scientists at the top of the network's pyramid rather than to the Chinese researchers who originated them.

And last month, developing-world members of the WHO's 34-country Executive Board complained at the board's annual meeting that the system routes viral isolates, and the vaccines that result from them, away from the developing countries that lack the capacity to manufacture them but are likely to need them the most.

"The pandemic will definitely occur in developing countries, not developed countries. But we are sending our virus (samples) to the rich countries to produce antivirals and vaccines. And when pandemic occurs, they survive and we die," Suwit Wibulpolprasert of Thailand said in remarks carried by Reuters.

"We are not opposing the sharing of information and virus, but on the condition that every country will have equal opportunity to get access to vaccine and anti-virals if such a pandemic occurs."

He was supported by Sameer Khalfan of Bahrain, who said: "There should be a fixed percentage of the vaccine produced for the pandemic strain for each region, proportionate to the population of each region, to ensure equitable and fair access."

At the end of the meeting, the board passed a resolution—to be sent to the full membership for a vote during May's World Health Assembly—that pointedly said: "No national influenza centre laboratory, Global Influenza Surveillance Collaborating Centre or H5 Reference Laboratory should charge fees or sell influenza viruses or strains or in any way seek to profit from participation in the WHO Global Influenza Surveillance Network. . . . No national, influenza centre laboratory, Global Influenza Surveillance Collaborating Centre or H5 Reference Laboratory should impose agreements or administrative procedures that may inhibit the proper functioning of the WHO Global Influenza Surveillance Network, including in particular the timely sharing of material and information."

Indonesia is a WHO member state but does not belong to the executive board.

In the teleconference Tuesday, Heymann said the virus-sharing relationship has broken down over twin concerns of intellectual property rights and vaccine access.

"Their major concern is that the virus strain they have put into the WHO network . . . has been used by several manufacturers to develop vaccines," he said. "Indonesia feels they must be getting some compensation for the use of their viruses in production and marketing of these vaccines."

In addition to intellectual property rights, Heymann said, the dispute hinges on the mismatch between where vaccine seed strains originate and where the vaccines that result from them are sold. Most vaccine manufacturers are in the industrialized world, whose countries are also the major markets for seasonal vaccine. If a pandemic strain arises and a vaccine can be developed against it, developing countries that also want to purchase it could find themselves at the end of a long queue.

"Developing countries . . . would like to have their own stockpiles, or would like to have some benefit from the viruses that they have given, seeing that there is not great access to vaccines in the world," Heymann said.

Indonesia is due Wednesday to sign a memorandum of understanding with vaccine manufacturer Baxter International. How much that memo could alter the relationship with the global flu-identification effort is unclear.

"We anticipate the MOU will then modify the way in which Indonesia participates in the network for sharing of novel influenza viruses," Heymann said. But Baxter told the Financial Times and Canadian Press today that the agreement would not block the sharing of Indonesian viral samples with others.

Whatever the memo's content, the issue of developing countries' desire to exert some self-protective control over flu-virus identification is unlikely to go away—as Heymann acknowledged Tuesday.

"The solution to this certainly comes from a round table at which many people are seated; that round table has to include pharmaceutical companies developing vaccines, it has to include countries that are having human infections, it has to have countries in whose interest it is to have those viruses and it has to have international organizations," he said. "We have begun those discussions with the pharmaceutical industry, with the governments, and we are gradually trying to come to a paradigm that will work."